Bridging the access gap: First-line blinatumumab for KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) in a public health system.

Abstract

e23441 Background: Infant acute lymphoblastic leukemia (ALL) accounts for approximately 4% of pediatric ALL and remains associated with poor outcomes, particularly in cases with KMT2A rearrangements. While event-free survival (EFS) in older children reaches 80–85%, infants continue to experience inferior survival and substantial treatment-related toxicity. Incorporation of blinatumomab in first-line therapy has emerged as a strategy to deepen remission, achieve minimal residual disease (MRD) negativity, reduce chemotherapy exposure, and optimize conditions for hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1). However, access to this therapy is limited in many low- and middle-income countries (LMICs), where cost remains a major barrier. Methods: We describe three infants with pro-B ALL harboring KMT2A::AFF1 rearrangements who received blinatumomab during CR1 within the Brazilian public health system (SUS), enabled through support from a nonprofit organization. Between November 2022 and June 2024, all patients received four cycles of blinatumomab. Ages at diagnosis were 5, 6, and 23 months, with initial white blood cell counts of 46,850/mm³, 1,073,000/mm³, and 635,000/mm³, respectively. All patients were CNS-1 and achieved CR1 prior to blinatumomab. Treatment backbones included AIEOP-BFM 2017 and Interfant-06 protocols. Results: All patients achieved and sustained MRD negativity at days 15 and 29 of blinatumomab. Treatment was well tolerated, with no adverse events above grade 1. Two patients proceeded to HSCT in CR1, while one remained in continuous remission without transplantation. All patients are alive and disease-free, with EFS ranging from 14 to 37 months. Conclusions: First-line blinatumomab was safe and effective in infants with KMT2A -rearranged ALL, enabling deep molecular responses with minimal toxicity and reduced reliance on intensive chemotherapy. This experience demonstrates that strategic partnerships with civil society organizations can overcome access barriers in public health systems, potentially lowering toxicity-related morbidity and downstream costs while delivering state-of-the-art care to highly vulnerable patients in LMICs.